Endoprosthesis coating

ABSTRACT

An endoprosthesis, such as a stent, includes anchoring regions formed of polymer that enhance adherence of a coating, e.g. a drug eluting polymer coating, to a stent surface, e.g. made of ceramic. The anchoring regions can be formed using stamping processes.

TECHNICAL FIELD

The invention relates to endoprosthesis coating.

BACKGROUND

The body includes various passageways including blood vessels such asarteries, and other body lumens. These passageways sometimes becomeoccluded or weakened. For example, they can be occluded by a tumor,restricted by plaque, or weakened by an aneurysm. When this occurs, thepassageway can be reopened or reinforced, or even replaced, with amedical endoprosthesis. An endoprosthesis is an artificial implant thatis typically placed in a passageway or lumen in the body. Manyendoprostheses are tubular members, examples of which include stents,stent-grafts, and covered stents.

Many endoprostheses can be delivered inside the body by a catheter.Typically the catheter supports a reduced-size or compacted form of theendoprosthesis as it is transported to a desired site in the body, forexample the site of weakening or occlusion in a body lumen. Uponreaching the desired site the endoprosthesis is installed so that it cancontact the walls of the lumen.

One method of installation involves expanding the endoprosthesis. Theexpansion mechanism used to install the endoprosthesis may includeforcing it to expand radially. For example, the expansion can beachieved with a catheter that carries a balloon in conjunction with aballoon-expandable endoprosthesis reduced in size relative to its finalform in the body. The balloon is inflated to deform and/or expand theendoprosthesis in order to fix it at a predetermined position in contactwith the lumen wall. The balloon can then be deflated, and the catheterwithdrawn. Stent delivery is further discussed in Heath, U.S. Pat. No.6,290,721.

SUMMARY

In an aspect, the invention features an endoprosthesis with a bodyincluding a ceramic on a surface thereof, a pattern of spaced polymericanchoring elements adhered to the ceramic, and a polymeric coatingadhered to the anchoring elements.

In another aspect, the invention features a method of forming anendoprosthesis including providing an endoprosthesis having a ceramic ona surface, applying to the surface an anchoring polymer, patterning theanchoring polymer to form anchors, and applying a polymer coating to theanchors.

Embodiments may include one or more of the following. The polymericcoating includes a drug. The ceramic is an oxide or nitride. The ceramicis IROX. The thickness of the anchoring elements is less than thethickness of the coating. The thickness of the anchoring elements isabout 10-90% of the thickness of the coating. The width of the anchoringelements is less than the height of the anchoring elements. Thethickness of the anchoring elements is about 1 to 10 micron. Theanchoring elements form a covalent bond to the ceramic. The anchoringelements are formed of silane. The anchoring elements includehydrophobic moieties.

Embodiments may also include one or more of the following. The polymericcoating is adhered to the anchoring elements without covalent bonding.The ceramic has a globular morphology. The ceramic has a defined grainmorphology. The anchoring elements extend into the ceramic. Theanchoring elements are substantially free of drug. The anchoring polymeris patterned by stamping to form regions of different thickness. Theanchoring polymer is patterned after stamping.

Embodiments may include one or more of the following advantages. Anendoprosthesis, such as a stent, can be provided with a polymer coating,such as a drug eluting coating, that is strongly adhered to the stent toreduce flaking or delamination. The stent can include a ceramicmaterial, and the polymer coating can be a material that has desirabledrug release characteristics but non-optimal adhesion characteristics tothe ceramic material. The adhesion can be enhanced without substantiallyincreasing the thickness of the polymer coating, or modifying its drugdelivery or biocompatibility characteristics. The stent can include apatterned first polymer directly on a ceramic surface, e.g. IROX, thathas good bonding characteristics to the ceramic. The pattern can be anintermittent series of separated lands that act as anchors. The first,anchor polymer also has good bonding characteristics to a secondpolymer. The second polymer is coated over the first polymer and anyexposed ceramic. The second polymer, e.g. a drug eluting polymer, isadhered strongly to the first polymer. The pattern and first polymeranchors expose a large surface for adherence to the second polymer andprovides a form fit for the second polymer.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

DESCRIPTION OF DRAWINGS

FIGS. 1A-1C are longitudinal cross-sectional views illustrating deliveryof a stent in a collapsed state, expansion of the stent, and deploymentof the stent.

FIG. 2A is a perspective view of a stent.

FIG. 2B is a cross sectional view of a portion of a stent wall.

FIGS. 3A-3I are cross-sectional views illustrating a method for forminga stent.

FIGS. 4A and 4B are plan views of morphologies.

FIGS. 5A-5C are schematics of morphologies.

FIG. 6 is a perspective view of a stent positioned to rotationallycontact a stamp.

FIG. 7 is a plan view illustrating anchoring patterns.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

Referring to FIGS. 1A-1C, a stent 20 is placed over a balloon 12 carriednear a distal end of a catheter 14, and is directed through the lumen 16(FIG. 1A) until the portion carry the balloon and stent reaches theregion of an occlusion 18. The stent 20 is then radially expanded byinflating the balloon 12 and compressed against the vessel wall with theresult that occlusion 18 is compressed, and the vessel wall surroundingit undergoes a radial expansion (FIG. 1B). The pressure is then releasedfrom the balloon and the catheter is withdrawn from the vessel (FIG.1C).

Referring to FIG. 2A, the stent 20 includes a plurality of fenestrations22 defined in a wall 23. Stent 22 includes several surface regions,including an outer, or abluminal, surface 24, an inner, or luminal,surface 26, and a plurality of cutface surfaces 28. The regions of thewall defining the fenestrations are sometimes referred to as stentstruts. The stent can be balloon expandable, as illustrated above, orself-expanding stent. In embodiments, the stent includes a body made ofe.g. a metal such as stainless steel, chrome, nickel, cobalt, tantalum,niobium (columbium), superelastic alloys such as nitiniol, cobaltchromium, MP35N, and other metals. Suitable stent materials and stentdesigns are described in Heath '721, supra.

Referring to FIG. 2B, a cross-section through a stent wall illustratingabluminal and luminal regions, the stent 20 includes a body 21, e.g. ametal. On the abluminal and adluminal surfaces 24, 26 of the body, thestent includes a layer 29 of a material effective to enhance stentfunction, such as a ceramic, e.g. Iridium dioxide (IROX), that enhancesstent endothelialization. The abluminal surface 24 further includes acoating 25 of a polymer that enhances function by, e.g. eluting a drug.The adherence of the coating 25 to the stent is enhanced by a pattern ofanchoring elements 27 which are bound tightly to the ceramic layer 29.The anchoring elements 27 are formed of a polymer with good adhesionproperties to both the ceramic and the polymer in the coating 25. Thepattern increases the surface area for bonding between the coating 25and the anchoring elements 27.

In embodiments, the anchoring elements 27 are formed of polymers such assilanes which can form Si—O bonds with a ceramic surface or havenon-covalently bonded adhesive interactions with the surface. Thesilanes can be modified for compatibility with the drug eluting polymercoating 25. For example, the silanes can be modified with moieties thatadjust hydrophobicity/hydrophilicity for compatibility with the polymercoating 25 or moieties that cross-link with the polymer coating 25.

In embodiments, the anchoring polymer can be a tie layer withhydrophyllic groups that adheres strongly to, e.g. a ceramic oxide, andhydrophobic groups that adhere to hydrophobic polymers suitable for drugrelease. Suitable polymers for anchoring elements 27 include the samepolymer as the drug eluting polymer coating. In embodiments, theanchoring elements 27 are formed of a different polymer than the drugeluting polymer coating. In embodiments, the anchoring elements aresubstantially free of drug, thus reducing the residual drug that remainson the stent. The anchoring elements can be covalently or non-covalentlybonded to the ceramic.

In embodiments, the anchoring elements 27 have a height, H_(a), of about10-80% of the thickness, T_(d), of the drug eluting polymer coating 25.The elements 27 have a width, W_(a), of about 10 to 200% of theirheight, H_(a). In embodiments, the height, H_(a), is about 1-10 micron.Formation of silane layer is discussed further in Duwez, NatureNanotechnology, 1, 122-125 (2006). A suitable drug eluting polymer isSIBS. Other suitable materials for layers 23, 25 and anchoring elementsare discussed below. Suitable polymers are described in U.S. patentapplication Ser. No. 11/776,304 filed contemporaneously herewith.

Referring to FIGS. 3A-3I, cross-sectional views of stent strut, atechnique for forming a stent is illustrated. Referring particularly toFIGS. 3A and 3B, the stent strut 30 includes a body 21 onto which isformed a coating 32 of ceramic, such as IROX. Referring to FIG. 3C, apolymeric coating is 34 is deposited over the coating 32 on a selectedside of the strut, such as the abluminal side. The coating 34 may be apolymer or a polymer precursor. Polymeric coating 34 is coated by, e.g,rolling, dipping or spraying.

Referring to FIG. 3D, the coating 34 is imprinted with a pattern by astamp 40. The stamp 40 has protrusions 42 which are brought into contactwith polymer coating, 34, e.g. while the polymer is still wet andmalleable. Referring specifically to FIG. 3E, stamp 40 is removed fromthe polymer coating 34 to reveal patterned polymer (or polymerprecursor) 36 containing surface relief features corresponding to theinverse of those of stamp 40. The patterned polymer is then dried orcured. Stamp 40 can be made of metal, ceramic, plastic, a relativelyhard polymer, or the like. For example, the stamp 40 can formed of asilicone elastomer, such as a polydimethylsiloxane. Protrusions 42 maytake a variety of desirable shapes, e.g. rectangular, circular, curved,etc., and may have straight or curved sidewalls. Protrusions 40 may alsobe formed of either continuous or discontinuous regions. The protrusionscan be formed by etching, laser ablation or molding. Techniques forforming patterns with small features are discussed in Rogers, U.S. Pat.Nos. 5,951,881 and 6,776,094. Contact patterning is discussed in U.S.Pat. No. 6,971,813.

Referring to FIG. 3F, the patterned polymer (or polymer precursor) 36 isetched, reducing the thickness of the polymer 36 and revealing portionsof the underlying coating 32. In embodiments, patterned polymer 36 isetched by a wet-chemical etchant 50. Suitable wet-chemical etchants mayinclude phosphoric, acetic, and nitric acids and water in a specificratio. In an alternative embodiment, polymer 36 may be removed by plasmaetching, e.g. with oxygen or ozon. With another alternative techniquepolymer 36 may be removed by use of laser ablation, for example byultrashort lasers or UV-excimer lasers. Other applicable processes forpolymer 36 removal may be ion bombardment or ion implantation. In otherembodiments, the patterned polymer is used without etching, etc. inwhich case regions of the ceramic are not exposed but rather a thinlayer of anchoring polymer remains between adjacent anchoring elements.

Referring particularly to FIG. 3G, the etching process forms a patternof anchoring elements 38, bonded to the coating 32. Referring to FIG.3H, a second polymer (or polymer precursor) 60 is coated over andform-fits around the anchoring elements. The polymer 60 can be dried,polymerized, and/or cross-linked to the anchoring elements.

Referring to FIG. 3I, in an alternative embodiment, the anchoringelements extend into wells 62 defined by the ceramic. The wells can beformed by, e.g. laser ablation etching after deposition of the ceramic(FIG. 3B).

The morphology and composition of the ceramic is selected for itsmechanical characteristics, to enhance adhesion to the stent body andenhance adhesion of a polymer coating, for example, and/or to enhancetherapeutic function such as reducing restenosis and enhancingendothelialization. Certain ceramics, e.g. oxides, can reduce restenosisthrough the catalytic reduction of hydrogen peroxide and otherprecursors to smooth muscle cell proliferation. The oxides can alsoencourage endothelial growth to enhance endothelialization of the stent.When a stent is introduced into a biological environment (e.g., invivo), one of the initial responses of the human body to theimplantation of a stent, particularly into the blood vessels, is theactivation of leukocytes, white blood cells which are one of theconstituent elements of the circulating blood system. This activationcauses a release of reactive oxygen compound production. One of thespecies released in this process is hydrogen peroxide, H₂O₂, which isreleased by neutrophil granulocytes, which constitute one of the manytypes of leukocytes. The presence of H₂O₂ may increase proliferation ofsmooth muscle cells and compromise endothelial cell function,stimulating the expression of surface binding proteins which enhance theattachment of more inflammatory cells. A ceramic such as iridium oxide(IROX) can catalytically reduce H₂O₂. The morphology of the ceramic canenhance the catalytic effect and reduce growth of endothelial cells.Iridium oxide (IROX) is discussed further in Alt, U.S. Pat. No.5,980,566. Defined grain morphologies may also allow for greater freedomof motion and are less likely to fracture as the stent is flexed in useand thus the coating resists delamination of the ceramic from anunderlying surface and reduces delamination of an overlaying polymercoating. The stresses caused by flexure of the stent, during expansionor contraction of the stent or as the stent is delivered through atortuously curved body lumen increase as a function of the distance fromthe stent axis. As a result, in embodiments, a morphology with definedgrains is particularly desirable on abluminal regions of the stent or atother high stress points, such as the regions adjacent fenestrationswhich undergo greater flexure during expansion or contraction.

The morphology of the surface of the ceramic is characterized by itsvisual appearance, its roughness, and/or the size and arrangement ofparticular morphological features such as local maxima. In embodiments,the surface is characterized by definable sub-micron sized grains.Referring particularly to FIG. 4A, for example, in embodiments, thegrains have a length, L, of the of about 50 to 500 nm, e.g. about100-300 nm, and a width, W, of about 5 nm to 50 nm, e.g. about 10-15 nm.The grains have an aspect ratio (length to width) of about 5:1 or more,e.g. 10:1 to 20:1. The grains overlap in one or more layers. Theseparation between grains can be about 1-50 nm. In particularembodiments, the grains resemble rice grains.

Referring particularly to FIG. 4B, in embodiments, the surface ischaracterized by a more continuous surface having a series of globularfeatures separated by striations. The striations have a width of about10 nm or less, e.g. 1 nm or less, e.g. 1 nm or about 0.1 nm. Thestriations can be generally randomly oriented and intersecting. Thedepth of the striations is about 10% or less of the thickness of thecoating, e.g. about 0.1 to 5%. In embodiments, the surface resembles anorange peel. In other embodiments, the surface has characteristicsbetween high aspect ratio definable grains and the more continuousglobular surface. For example, the surface can include low aspect ratiolobes or thin planar flakes. The morphology type is visible in FESEMimages at 50 KX.

The roughness of the surface is characterized by the average roughness,Sa, the root mean square roughness, Sq, and/or the developed interfacialarea ratio, Sdr. The Sa and Sq parameters represent an overall measureof the texture of the surface. Sa and Sq are relatively insensitive indifferentiating peaks, valleys and the spacing of the various texturefeatures. Surfaces with different visual morphologies can have similarSa and Sq values. For a surface type, the Sa and Sq parameters indicatesignificant deviations in the texture characteristics. Sdr is expressedas the percentage of additional surface area contributed by the textureas compared to an ideal plane the size of the measurement region. Sdrfurther differentiates surfaces of similar amplitudes and averageroughness. Typically Sdr will increase with the spatial intricacy of thetexture whether or not Sa changes.

In embodiments, the ceramic has a defined grain type morphology. The Sdris about 30 or more, e.g. about 40 to 60. In addition or in thealternative, the morphology has an Sq of about 15 or more, e.g. about 20to 30. In embodiments, the Sdr is about 100 or more and the Sq is about15 or more. In other embodiments, the ceramic has a globular typesurface morphology. The Sdr is about 20 or less, e.g. about 8 to 15. TheSq is about 15 or less, e.g. about less than 8 to 14. In still otherembodiments, the ceramic has a morphology between the defined grain andthe globular surface, and Sdr and Sq values between the ranges above,e.g. an Sdr of about 1 to 200 and/or an Sq of about 1 to 30.

Referring to FIGS. 5A-5C, morphologies are also characterized by thesize and arrangement of morphological features such as the spacing,height and width of local morphological maxima. Referring particularlyto FIG. 5A, a coating 40 on a substrate 42 is characterized by thecenter-to-center distance and/or height, and/or diameter and/or densityof local maxima. In particular embodiments, the average height, distanceand diameter are in the range of about 400 nm or less, e.g. about 20-200nm. In particular, the average center-to-center distance is about 0.5 to2× the diameter.

Referring to FIG. 5B, in particular embodiments, the morphology type isa globular morphology, the width of local maxima is in the range ofabout 100 nm or less and the peak height is about 20 nm or less. Inparticular embodiments, the ceramic has a peak height of less than about5 nm, e.g., about 1-5 nm, and/or a peak distance less than about 15 nm,e.g., about 10-15 nm. Referring to FIG. 5C, in embodiments, themorphology is defined as a grain type morphology. The width of localmaxima is about 400 nm or less, e.g. about 100-400 nm, and the height oflocal maxima is about 400 nm or less, e.g. about 100-400 nm. Asillustrated in FIGS. 5B and 5C, the select morphologies of the ceramiccan be formed on a thin layer of substantially uniform, generallyamorphous IROX, which is in turn formed on a layer of iridium metal,which is in turn deposited on a metal substrate, such as titanium orstainless steel. The spacing, height and width parameters can becalculated from AFM data.

Further discussion of morphologies and a suitable computationaltechnique is provided in U.S. patent application Ser. Nos. 11/752,772and 11/752,736, filed May 23, 2007. Suitable ceramics include metaloxides and nitrides, such as of iridium, zirconium, titanium, hafnium,niobium, tantalum, ruthenium, platinum and aluminum. The ceramic can becrystalline, partly crystalline or amorphous. The ceramic can be formedentirely of inorganic materials or a blend of inorganic and organicmaterial (e.g. a polymer). In other embodiments, the morphologiesdescribed herein can be formed of metal. In embodiments, the thickness Tof the coatings is in the range of about 50 nm to about 2 um, e.g. 100nm to 500 nm.

Referring to FIG. 6, a system for imprinting a pattern includes arotatable cylinder 70 with a pattern of protrusions 72. The cylinder 70is placed into proximity with a stent 20 mounted for rotation such that,upon rotation (arrows) of the cylinder 70 and the stent 20, theprotrusions imprint a pattern on the stent. Referring to FIG. 7,exemplary patterns are illustrated. Nonlinear patterns, e.g. sinsordialwave patterns can be implemented. The pattern can also be anon-repeating random series of protrusions of various shapes and atvarious positions.

Suitable polymers for the anchoring elements and/or the drug elutingpolymers are described in U.S. patent application Ser. No. 11/776,304,filed contemporaneously herewith. Similar polymers may be hydrophilic orhydrophobic, and may be selected, without limitation, from polymersincluding, for example, polycarboxylic acids, cellulosic polymers,including cellulose acetate and cellulose nitrate, gelatin,polyvinylpyrrolidone, cross-linkedpolyvinylpyrrolidone, polyanhydridesincluding maleic anhydride polymers, polyamides, polyvinyl alcohols,copolymers of vinyl monomers such as EVA, polyvinyl ethers, polyvinylaromatics such as polystyrene and copolymers thereof with other vinylmonomers such as isobutylene, isoprene and butadiene, for example,styrene-isobutylene-styrene (SIBS) copolymers, styrene-isoprene-styrene(SIS) copolymers, styrene-butadiene-styrene (SBS) copolymers,polyethylene oxides, glycosaminoglycans, polysaccharides, polyestersincluding polyethylene terephthalate, polyacrylamides, polyethers,polyether sulfone, polycarbonate, polyalkylenes including polypropylene,polyethylene and high molecular weight polyethylene, halogeneratedpolyalkylenes including polytetrafluoroethylene, natural and syntheticrubbers including polyisoprene, polybutadiene, polyisobutylene andcopolymers thereof with other vinyl monomers such as styrene,polyurethanes, polyorthoesters, proteins, polypeptides, silicones,siloxane polymers, polylactic acid, polyglycolic acid, polycaprolactone,polyhydroxybutyrate valerate and blends and copolymers thereof as wellas other biodegradable, bioabsorbable and biostable polymers andcopolymers. Coatings from polymer dispersions such as polyurethanedispersions (BAYHDROL®, etc.) and acrylic latex dispersions are alsowithin the scope of the present invention. The polymer may be a proteinpolymer, fibrin, collage and derivatives thereof, polysaccharides suchas celluloses, starches, dextrans, alginates and derivatives of thesepolysaccharides, an extracellular matrix component, hyaluronic acid, oranother biologic agent or a suitable mixture of any of these, forexample. In one embodiment, the preferred polymer is polyacrylic acid,available as HYDROPLUS® (Boston Scientific Corporation, Natick, Mass.),and described in U.S. Pat. No. 5,091,205, the disclosure of which ishereby incorporated herein by reference. U.S. Pat. No. 5,091,205describes medical devices coated with one or more polyiocyanates suchthat the devices become instantly lubricious when exposed to bodyfluids. In another preferred embodiment of the invention, the polymer isa copolymer of polylactic acid and polycaprolactone. Suitable polymersare discussed in U.S. Publication No. 20060038027.

The polymer is preferably capable of absorbing a substantial amount ofdrug solution. When applied as a coating on a medical device inaccordance with the present invention, the dry polymer is typically onthe order of from about 1 to about 50 microns thick. In the case of aballoon catheter, the thickness is preferably about 1 to 10 micronsthick, and more preferably about 2 to 5 microns. Very thin polymercoatings, e.g., of about 0.2-0.3 microns and much thicker coatings,e.g., more than 10 microns, are also possible. It is also within thescope of the present invention to apply multiple layers of polymercoating onto a medical device. Such multiple layers are of the same ordifferent polymer materials.

The terms “therapeutic agent”, “pharmaceutically active agent”,“pharmaceutically active material”, “pharmaceutically activeingredient”, “drug” and other related terms may be used interchangeablyherein and include, but are not limited to, small organic molecules,peptides, oligopeptides, proteins, nucleic acids, oligonucleotides,genetic therapeutic agents, non-genetic therapeutic agents, vectors fordelivery of genetic therapeutic agents, cells, and therapeutic agentsidentified as candidates for vascular treatment regimens, for example,as agents that reduce or inhibit restenosis. By small organic moleculeis meant an organic molecule having 50 or fewer carbon atoms, and fewerthan 100 non-hydrogen atoms in total.

Exemplary therapeutic agents include, e.g., anti-thrombogenic agents(e.g., heparin); anti-proliferative/anti-mitotic agents (e.g.,paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine,inhibitors of smooth muscle cell proliferation (e.g., monoclonalantibodies), and thymidine kinase inhibitors); antioxidants;anti-inflammatory agents (e.g., dexamethasone, prednisolone,corticosterone); anesthetic agents (e.g., lidocaine, bupivacaine andropivacaine); anti-coagulants; antibiotics (e.g., erythromycin,triclosan, cephalosporins, and aminoglycosides); agents that stimulateendothelial cell growth and/or attachment. Therapeutic agents can benonionic, or they can be anionic and/or cationic in nature. Therapeuticagents can be used singularly, or in combination. Preferred therapeuticagents include inhibitors of restenosis (e.g., paclitaxel),anti-proliferative agents (e.g., cisplatin), and antibiotics (e.g.,erythromycin). Additional examples of therapeutic agents are describedin U.S. Published Patent Application No. 2005/0216074. Polymers for drugelution coatings are also disclosed in U.S. Published Patent ApplicationNo. 2005/019265A.

Suitable materials for layer 23 include coatings that enhancebiocompatibility, reduce proliferation, and facilitateendothelialization. Materials include ceramics, such as ceramic oxidesand nitrides of iridium, titanium, and zirconium. The ceramics can beformed by sputtering or wet chemical techniques. A particular oxide isIROX which is further discussed in U.S. Pat. No. 5,980,566 and U.S. Ser.No. 10/651,562 filed Aug. 29, 2003. The layer 23 can be, e.g. 10-1000 nmin thickness.

In embodiments, the anchoring elements and layer 23 are provided only onthe abluminal surface, as illustrated. In other embodiments, theseelements are provided as well or only on the abluminal surface and/orcut-face surfaces.

The stents described herein can be configured for vascular, e.g.coronary and peripheral vasculature or non-vascular lumens. For example,they can be configured for use in the esophagus or the prostate. Otherlumens include biliary lumens, hepatic lumens, pancreatic lumens,uretheral lumens and ureteral lumens.

Any stent described herein can be dyed or rendered radio-opaque byaddition of, e.g., radio-opaque materials such as barium sulfate,platinum or gold, or by coating with a radio-opaque material. Inembodiments, the porous structure can be formed directly on the stentbody, as described above, or the porous structure can be formed in acoating over the stent body. The coating may be, e.g., a radio-opaquemetal.

The stent can include (e.g., be manufactured from) metallic materials,such as stainless steel (e.g., 316L, BioDur® 108 (UNS S29108), and 304Lstainless steel, and an alloy including stainless steel and 5-60% byweight of one or more radiopaque elements (e.g., Pt, Ir, Au, W) (PERSS®)as described in US-2003-0018380-A1, US-2002-0144757-A1, andUS-2003-0077200-A1), Nitinol (a nickel-titanium alloy), cobalt alloyssuch as Elgiloy, L605 alloys, MP35N, titanium, titanium alloys (e.g.,Ti-6Al-4V, Ti-50Ta, Ti-10Ir), platinum, platinum alloys, niobium,niobium alloys (e.g., Nb-1Zr) Co-28Cr-6Mo, tantalum, and tantalumalloys. Other examples of materials are described in commonly assignedU.S. application Ser. No. 10/672,891, filed Sep. 26, 2003; and U.S.application Ser. No. 11/035,316, filed Jan. 3, 2005. Other materialsinclude elastic biocompatible metal such as a superelastic orpseudo-elastic metal alloy, as described, for example, in Schetsky, L.McDonald, “Shape Memory Alloys”, Encyclopedia of Chemical Technology(3rd ed.), John Wiley & Sons, 1982, vol. 20. pp. 726-736; and commonlyassigned U.S. application Ser. No. 10/346,487, filed Jan. 17, 2003.

The stent can be of a desired shape and size (e.g., coronary stents,aortic stents, peripheral vascular stents, gastrointestinal stents,urology stents, tracheal/bronchial stents, and neurology stents).Depending on the application, the stent can have a diameter of between,e.g., about 1 mm to about 46 mm. In certain embodiments, a coronarystent can have an expanded diameter of from about 2 mm to about 6 mm. Insome embodiments, a peripheral stent can have an expanded diameter offrom about 4 mm to about 24 mm. In certain embodiments, agastrointestinal and/or urology stent can have an expanded diameter offrom about 6 mm to about 30 mm. In some embodiments, a neurology stentcan have an expanded diameter of from about 1 mm to about 12 mm. Anabdominal aortic aneurysm (AAA) stent and a thoracic aortic aneurysm(TAA) stent can have a diameter from about 20 mm to about 46 mm. Thestent can be balloon-expandable, self-expandable, or a combination ofboth (e.g., U.S. Pat. No. 6,290,721).

All publications, patent applications, patents, and other referencesmentioned herein are incorporated by reference herein in their entirety.

Still further embodiments are in the following claims.

1. An endoprosthesis, comprising: a body including a ceramic on asurface thereof a pattern of spaced polymeric anchoring elements adheredto the ceramic, and a polymeric coating adhered to the anchoringelements, the polymeric coating having an enhanced adherence to theceramic through the anchoring elements and having a thickness greaterthan a thickness of the anchoring elements.
 2. The endoprosthesis ofclaim 1, wherein the polymeric coating includes a drug.
 3. Theendoprosthesis of claim 1, wherein the ceramic is free of a polymerforming the polymeric anchoring elements.
 4. The endoprosthesis of claim1, wherein the anchoring elements extend into wells defined in theceramic.
 5. The endoprosthesis of claim 1, wherein the ceramic is anoxide or nitride.
 6. The endoprosthesis of claim 1, wherein the ceramicis IROX.
 7. The endoprosthesis of claim 1, wherein the thickness of theanchoring elements is about 10-90% of the thickness of the coating. 8.The endoprosthesis of claim 1, wherein the width of the anchoringelements is less than the height of the anchoring elements.
 9. Theendoprosthesis of claim 1, wherein the thickness of the anchoringelements is about 1 to 10 micron.
 10. The endoprosthesis of claim 1,wherein the anchoring elements form a covalent bond to the ceramic. 11.The endoprosthesis of claim 10, wherein the anchoring elements areformed of silane.
 12. The endoprosthesis of claim 10, wherein theanchoring elements include hydrophobic moieties.
 13. The endoprosthesisof claim 1, wherein the polymeric coating is adhered to the anchoringelements without covalent bonding.
 14. The endoprosthesis of claim 1,wherein the ceramic has a globular morphology.
 15. The endoprosthesis ofclaim 1, wherein the ceramic has a defined grain morphology.
 16. Theendoprosthesis of claim 1, wherein the anchoring elements extend intothe ceramic.
 17. The endoprosthesis of claim 1, wherein the anchoringelements are substantially free of drug.
 18. A method of forming anendoprosthesis, comprising: providing an endoprosthesis including aceramic on a surface, applying to the ceramic on the surface ananchoring polymer, patterning the anchoring polymer to form anchors,applying a polymer coating to the anchors, the polymer coating having anenhanced adhesion to the ceramic through the anchors and having athickness greater than a thickness of the anchors.
 19. The method ofclaim 18, comprising patterning the anchoring polymer by stamping toform regions of different thickness.
 20. The method of claim 19,comprising etching the anchoring polymer after stamping.
 21. The methodof claim 18, wherein the polymeric coating includes a drug.
 22. Themethod of claim 18, wherein the ceramic is IROX.
 23. The method of claim18, wherein the thickness of the anchoring element is about 1 to 10micron.
 24. The method of claim 18, wherein the polymer coating isadhered to the anchoring elements without covalent bonding.
 25. Anendoprosthesis, comprising: a body including a ceramic on a surfacethereof a pattern of spaced polymeric anchoring elements adhered to theceramic, and a polymeric coating adhered to the anchoring elements, theanchoring elements being formed of silane and forming a covalent bond tothe ceramic.
 26. A method of forming an endoprosthesis, comprising:providing an endoprosthesis including a ceramic on a surface, applyingto the ceramic on the surface an anchoring polymer, patterning theanchoring polymer to form anchors by stamping to form regions ofdifferent thickness, applying a polymer coating to the anchors.